英國(guó)《自然》（Nature）雜志8月24日發(fā)表的一項(xiàng)研究結(jié)果顯示,，一種名為ALK的基因發(fā)生變異，會(huì)增加兒童患神經(jīng)母細(xì)胞瘤的風(fēng)險(xiǎn),。
來自美國(guó),、意大利和比利時(shí)的研究人員介紹說，他們對(duì)20個(gè)家庭進(jìn)行了研究,，其中每個(gè)家庭有一名以上的兒童患神經(jīng)母細(xì)胞瘤,。研究發(fā)現(xiàn)，ALK基因發(fā)生特定變異后會(huì)持續(xù)處于活躍狀態(tài),，從而促進(jìn)細(xì)胞的增殖,。細(xì)胞不受控制地增殖，通常是癌癥發(fā)病的標(biāo)志,。
神經(jīng)母細(xì)胞瘤是一種較為罕見的兒童癌癥，它會(huì)損傷兒童的神經(jīng)系統(tǒng),，兒童患上這種癌癥的存活率僅有40%,。
研究人員認(rèn)為，新研究成果將有助于從遺傳角度加深對(duì)兒童神經(jīng)母細(xì)胞瘤的認(rèn)識(shí),，同時(shí)也為開發(fā)診斷和治療這種疾病的新方法提供了線索,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature,，doi:10.1038/nature07261，Ya?l P. Mossé, John M. Maris
Identification of ALK as a major familial neuroblastoma predisposition gene
Yaël P. Mossé1, Marci Laudenslager1, Luca Longo2, Kristina A. Cole1, Andrew Wood1, Edward F. Attiyeh1, Michael J. Laquaglia1, Rachel Sennett1, Jill E. Lynch1, Patrizia Perri2,3, Geneviève Laureys4, Frank Speleman4, Cecilia Kim5, Cuiping Hou1,5, Hakon Hakonarson5,7, Ali Torkamani6, Nicholas J. Schork6, Garrett M. Brodeur1, Gian P. Tonini2, Eric Rappaport1, Marcella Devoto7,8 & John M. Maris1,9
Neuroblastoma is a childhood cancer that can be inherited, but the genetic aetiology is largely unknown. Here we show that germline mutations in the anaplastic lymphoma kinase (ALK) gene explain most hereditary neuroblastomas, and that activating mutations can also be somatically acquired. We first identified a significant linkage signal at chromosome bands 2p23–24 using a whole-genome scan in neuroblastoma pedigrees. Resequencing of regional candidate genes identified three separate germline missense mutations in the tyrosine kinase domain of ALK that segregated with the disease in eight separate families. Resequencing in 194 high-risk neuroblastoma samples showed somatically acquired mutations in the tyrosine kinase domain in 12.4% of samples. Nine of the ten mutations map to critical regions of the kinase domain and were predicted, with high probability, to be oncogenic drivers. Mutations resulted in constitutive phosphorylation, and targeted knockdown of ALK messenger RNA resulted in profound inhibition of growth in all cell lines harbouring mutant or amplified ALK, as well as in two out of six wild-type cell lines for ALK. Our results demonstrate that heritable mutations of ALK are the main cause of familial neuroblastoma, and that germline or acquired activation of this cell-surface kinase is a tractable therapeutic target for this lethal paediatric malignancy
